Many anticancer drugs are currently available for treating various types of cancers in the clinic, but their therapeutic efficacy has been limited by the inability to selectively deliver these drugs to the tumors. Most, if not all, of these anticancer drugs are highly cytotoxic and can kill normal cells along with the cancerous cells. Because of the lack of methods to deliver these anticancer drugs to the tumor regions, a high dose of these drugs is often needed, which can cause undesirable side effects. As a result, most of the currently used anticancer drugs have a rather limited therapeutic index. Such a limit on the dosage prevents the complete eradication of all the cancer cells in a patient, and can lead to the recurrence of the cancer in many patients. The limit in dosage can also predispose the recurring cancer to drug resistance and thus worsens the prognosis of the patient. There is therefore a great need for new anticancer compositions that can be selectively delivered to the tumors and provide superior therapeutic indices. There is also a need for real-time techniques for directly monitoring how efficiently the anticancer drugs are localized in tumors after their administration.
Bisphosphonates, such as those shown below in Scheme 1, have been used to treat bone resorption-related diseases, such as osteoporosis. Recently, bisphosphonates (in particular, zoledronic acid and pamidronate) have been used to treat bone metastases of several cancers such as breast cancer. There is also increasing evidence that bisphosphonates can be effective antitumor agents by blocking metalloproteinase and other important protein pathways. However, the clinical application of bisphosphonates as anticancer therapeutics is limited by their unfavorable pharmacokinetics as the majority of the injected phosphonates either bind to the bones or are quickly cleared via kidney filtration. Accordingly, there is a need for additional methods of delivering bisphosphonates as therapeutic agents, such as for treating cancer and bone-related disorders.